Noguchi Yukiko, Ohtake Akiyoshi, Suzuki Masanori, Sasamata Masao
Pharmacology Research Labs., Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan.
Eur J Pharmacol. 2008 Feb 2;580(1-2):256-61. doi: 10.1016/j.ejphar.2007.11.003. Epub 2007 Nov 13.
Alpha-adrenoceptor antagonists are used worldwide for the treatment of voiding dysfunction associated with benign prostatic hyperplasia. Recently, abnormal ejaculation, an adverse effect associated with their use, has attracted attention. Here, we simultaneously investigated the effects of alpha(1)-adrenoceptor antagonists on intraurethral pressure in the prostatic urethra and intraluminal pressure in the vas deferens in anesthetized male dogs, and compared their tissue selectivity. Phenylephrine, an alpha(1)-adrenoceptor agonist, induced simultaneous increases in intraurethral and intraluminal pressure. Alfuzosin, naftopidil, prazosin, silodosin and tamsulosin dose-dependently inhibited both responses. Comparison of ED(50) values in both tissues showed that silodosin had the highest selectivity for the vas deferens (7.5-fold), followed by naftopidil (4.3-fold), alfuzosin (3.8-fold), tamsulosin (2.6-fold) and prazosin (2.5-fold). These results suggest that alpha(1)-adrenoceptor antagonists inhibit contraction of not only the urethra but also the vas deferens in a dose-dependent fashion, and that their high tissue selectivity for the vas deferens over the urethra may contribute to the incidence of abnormal ejaculation.
α-肾上腺素能受体拮抗剂在全球范围内用于治疗与良性前列腺增生相关的排尿功能障碍。最近，与其使用相关的不良反应——异常射精引起了关注。在此，我们同时研究了α(1)-肾上腺素能受体拮抗剂对麻醉雄性犬前列腺尿道内尿道压力和输精管腔内压力的影响，并比较了它们的组织选择性。α(1)-肾上腺素能受体激动剂去氧肾上腺素可引起尿道内压力和腔内压力同时升高。阿夫唑嗪、萘哌地尔、哌唑嗪、西洛多辛和坦索罗辛均剂量依赖性地抑制这两种反应。两种组织中ED(50)值的比较表明，西洛多辛对输精管的选择性最高(7.5倍)，其次是萘哌地尔(4.3倍)、阿夫唑嗪(3.8倍)、坦索罗辛(2.6倍)和哌唑嗪(2.5倍)。这些结果表明，α(1)-肾上腺素能受体拮抗剂不仅能剂量依赖性地抑制尿道收缩，还能抑制输精管收缩，并且它们对输精管相对于尿道的高组织选择性可能与异常射精的发生率有关。
